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Jie Yang, Yongyun Li, Chunyan Zong, Qianqian Zhang, Shengfang Ge, Lei Ma, Jiayan Fan, Jianming Zhang, Renbing Jia; Xanthatin Selectively Targets Retinoblastoma by Inhibiting the PLK1-Mediated Cell Cycle. Invest. Ophthalmol. Vis. Sci. 2021;62(15):11. doi: https://doi.org/10.1167/iovs.62.15.11.
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Retinoblastoma is the most common primary intraocular malignant tumor in children. Although intra-arterial chemotherapy and conventional chemotherapy have become promising therapeutic approaches for advanced intraocular retinoblastoma, the side effects threaten health and are unavoidable, making the development of targeted therapy an urgent need. Therefore, we intended to find a potential drug for human retinoblastoma by screening an in-house compound library that included 89 purified and well-characterized natural products.
We screened a panel of 89 natural products in retinoblastoma cell lines to find the inhibitor. The inhibition of the identified inhibitor xanthatin on cell growth was detected through half-maximal inhibitory concentration (IC50), flow cytometry assay, and zebrafish model system. RNA-seq further selected the target gene PLK1.
We reported the discovery of xanthatin as an effective inhibitor of retinoblastoma. Mechanistically, xanthatin selectively inhibited the proliferation of retinoblastoma cells by inducing cell cycle arrest and promoting apoptosis. Interestingly, xanthatin targeted PLK1-mediated cell cycle progression. The efficacy of xanthatin was further confirmed in zebrafish models.
Collectively, our data suggested that xanthatin significantly inhibited tumor growth in vitro and in vivo, and xanthatin could be a potential drug treatment for retinoblastoma.
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